DESCRIPTION (Verbatim from the Applicant's Abstract): Despite the widespread success and enthusiasm f single and double lung transplantation, demand for donor lungs has steadily outgrown supply. Currently, the average wait is two years, with 30 percent wait-list mortality. A prototype Paracorporeal Artificial Lung (PAL) was designed and built by MC3 (Ann Arbor, MI) for high gas exchange efficiency and very low blood flow resistance. The initial PAL was implanted by our collaborators (UTMB) in a pulmonary artery-to-pulmonary artery (PA-PA) configuration, and supported gas exchange in normal sheep (N=8) for up to 7 days. Mean pressure gradient at total PA flow across the artificial lung was 8 mm Hg (3 Wood units); 4 of 8 sheep survived complete balloon inflation (full flow) but 4 of 8 sheep were intolerant from right heart failure. Complications included exsanguination (4/8) due to breakage (2 sample ports, 2-cannula disconnection). Therefore, necessary prototype PAL modifications include: 1) a lower resistance gas exchanger with 2) an inflow compliance chamber, and 3) collet-nut cannula connections without blood sample ports. The immediate goal of this research plan is to: Specific Aim 1. Build a working prototype for the modified PAL, based on our initial experience, to incorporate the following design changes 1) lower resistance gas exchanger with 2) inflow compliance chamber and 3) collet-nut cannula connections without blood sample ports. Specific Aim 2. a) Perform 7-day studies in healthy sheep to determine the maximum level of PAL gas exchange performance and hemodynamic augmentation achievable. b) We will utilize our recently developed, clinically relevant (LD50) model of acute respiratory distress syndrome (ARDS) in adult sheep (n=8) to initially evaluate PAL performance during acute respiratory distress syndrome (ARDS) for seven days. For Phase II, we will perform a prospective, randomized outcomes study comparing standardized pressure controlled mechanical ventilation versus PAL in our LD50 and LD100 models of ARDS to determine long-term survival or bridge capability during severe respiratory failure. This project will complete the PAL development and yield patient management and selection protocols for future PAL human safety trials. PROPOSED COMMERCIAL APPLICATION: The commercial potential for the PAL is both immediate and has the potential for significant spin-off technology. The immediate market will be as a bridge to lung transplant. The long term potential is as an alternative to transplant for end-stage lung disease (a much larger population). The research proposed will also undoubtedly benefit the design of routine cardiopulmonary bypass (CPB) oxygenators (300,000 cases a year in the U.S. alone at a market price of $90,000,000).